Basic science for clinicians.

605 The earliest description of calcific aortic stenosis is attributed to the French physician Lazare Rivière who, in 1663, reported the necropsy findings from a patient with palpitations, progressive dyspnea, and loss of peripheral pulses. He noted left ventricular enlargement and identified large caruncle-like masses obstructing the left ventricular outflow to the aorta. Although other reports followed, the debate about the etiology of aortic valve calcification (AVC) did not begin until much later. Although calcification was originally attributed to endocarditis, in 1846, Hasse challenged this theory by suggesting that a degenerative process occurred within the valve itself to initiate ossification. In 1904, Möenckeburg authored the first detailed description of AVC in which he reported that this pathology likely occurred as a result of calcium deposition on valve cusps that had become sclerotic. He described 2 mechanisms to explain this phenomenon: degeneration within the layers of the valve leaflets nearest the sinuses of Valsalva that propagated toward the tips of the cusps or sclerotic changes of the aorta that extended to involve the valve cusps. Within the past 20 years, there has been a tremendous resurgence in interest in advancing these early hypotheses to identify the cellular and molecular mechanisms that initiate AVC owing to the high prevalence of this disease, its associated morbidity and mortality, and the emerging idea that therapies that target these processes could increase the durability of surgically implanted and transcatheter bioprosthetic valves.